Red blood cell (RBC) transfusions are the cornerstone of supportive care in patients with myelodysplastic syndromes (MDS). While transfusions alleviate symptomatic anemia, they inevitably lead to progressive iron accumulation in patients. This transfusional iron overload may exert toxic effects on the heart, liver, endocrine system, ultimately contributing to increased morbidity and mortality. Timely initiation of iron chelation therapy has become an important consideration in the comprehensive management of MDS.

Chelation is primarily indicated for patients with lower-risk MDS (IPSS low or Int-1) who are expected to have longer survival, who remain transfusion-dependent. In such patients, iron overload not only threatens organ function also worsens prognosis. Multiple studies have shown that transfusion dependence is a negative prognostic factor, and retrospective analyses suggest that iron chelation may improve overall survival. Chelation is also particularly important in patients who are candidates for allogeneic stem cell transplantation, since excess iron has been associated with inferior transplant outcomes. By reducing systemic iron burden, chelation help optimize organ function and improve transplant eligibility.

The decision is usually guided by transfusion history and serum ferritin levels. Most guidelines recommend considering chelation after approximately 20–30 units of RBC transfusions or when serum ferritin persistently exceeds 2500 ng/mL. The therapeutic goal is to maintain ferritin below 1000 ng/mL, minimizing iron-mediated oxidative stress and tissue damage. While serum ferritin is an imperfect surrogate, it remains a practical marker. More advanced techniques such as MRI T2* or SQUID can provide direct estimates of hepatic iron, but their availability is limited.

Three chelators are currently in clinical use. Deferoxamine, administered subcutaneously or intramuscularly, is effective but limited by its parenteral route. Deferasirox, an oral once-daily agent, has become the preferred choice in many cases and is FDA-approved for transfusion-related iron overload. Randomized trials in lower-risk MDS demonstrated that deferasirox reduced ferritin, improved event-free survival, and even enhanced hematologic response in some patients. However, renal, hepatic toxicity require careful monitoring. Deferiprone, another oral agent, is mainly approved for thalassemia, can be considered when other chelators fail, though its use in MDS remains limited due to risk of agranulocytosis.

Chelation has been associated with improved overall survival in observational studies, prospective trials provide encouraging evidence. Beyond survival, reversal of some iron-related cardiac, hepatic damage has been documented, underscoring its importance. Monitoring should include serial ferritin, renal, liver function, vigilance for adverse events. Individualization is critical: patients with advanced or high-risk MDS, limited life expectancy are less likely to benefit, and chelation is generally not recommended in such settings.

Iron chelation therapy plays a vital role in selected MDS patients. It should be considered in lower-risk individuals with substantial transfusion requirements and elevated ferritin, especially in those with preserved organ function or who are candidates for transplantation. As evidence grows, iron chelation continues to evolve from a supportive measure into a prognostically meaningful intervention in the management of MDS.